The membrane of the biological cell, consisting of amphiphilic glycolipids, phospholipids, cholesterol and proteins, is the outermost boundary that separates the intracellular components from the extracellular environment and is involved in a wide variety of biological processes. It is semipermeable and capable of regulating what enters and exits the cell. The transport of substances in and out of the cell can take place with or without active participation of the cell membrane. The surface of the cell membrane anchors the cytoskeleton and the other molecules that activate or deactivate certain cell processes. Proteins embedded in the membrane act as selective channels for ions, receptors for information exchange between cells and organelles, and take part in activities such as immune response and cell adhesion. The membrane and the proteins carry out these functions mainly by changing their structure reversibly. How these structural changes take place and the molecular mechanisms behind them are at the forefront of life science research.
The structure of the generally accepted fluid mosaic model of the membrane is a self assembling two dimensional smectic liquid crystalline amphiphilic lipid bilayer in which hydrophobic hydrocarbon chains are inside and hydrophilic polar headgroups are outside. However, recent studies show that cell membranes contain different structures or domains that can be classified as protein-protein complexes; lipid rafts, pickets and fences formed by the actin-based cytoskeleton; and other large stable structures, such as synapses or desmosomes.
The phase behavior of lipids in the membrane is known to be involved in cell fusion processes and membrane traffic, for example, during exocytosis or virus-cell fusion in the course of an infection. The propagation of action potential in nerve and muscle cell and retinal photoreceptors have been attributed to the ferroelectric properties arising from chiral building blocks. A Curie point and current-voltage hysteresis typical of ferroelectric substances have been observed in cell membranes. Temperature dependent current has been induced by laser in frog of ranvier suggesting a pyroelectric effect. Swelling of membranes in response to a voltage application, which indicates a piezoelectric effect, has been reported. It has been suggested that ferroelectricity may be common in cell components and a relationship between liquid crystalline ferroelectricity and nerve and muscle impulses has been predicted, but so far the possible origin of the ferroelectric structure in the cell membrane has not been demonstrated.
Both glycolipids and phospholipids contain polar (hydrophilic) head groups and apolar (hydrophobic) alkyl chains. They are quite similar in their molecular shape and phase behavior. They are amphotropic liquid crystals: they form thermotropic liquid crystalline phases in their pure form as the temperature is varied and lyotropic liquid crystalline phases in solvent as the concentration is varied. The length of the alkyl chain and the number of head groups determine the polymorphism in both thermotropic and lyotropic structures. They form smectic bilayers in water at a critical concentration of lipids. Lyotropic properties of both glycolipids and phospholipids have been extensively studied in the last decade but so far their thermotropic properties have not been assessed properly. The thermotropic form of membrane lipids, both phospholipids and glycolipids, presents a unique opportunity to investigate many of their physical especially electrical properties which are more difficult to study in aqueous systems. Most membrane lipids with two long alkyl chains form only a columnar phase in their pure form. A smectic phase of these membrane lipids can be induced by mixing them with amphiphilic lipids which form only a smectic phase, providing ideal systems to investigate structural and electrical properties of lipid bilayers.
Recently it was shown based on dielectric and X-ray diffraction studies, and optical microscopic observations that the glycolipid molecules are tilted in their bilayers in the smectic phase but the direction of the tilt is varied from one bilayer to the next. Large numbers of studied synthetic glycolipids with varying chemical structures exhibited quite similar behavior. The tilted supramolecular structures they from in both bent-core and straight-core liquid crystals also show that lipid molecules are tilted in the bilayers. The bilayers of tilted chiral glycolipid molecules are electrically polarized. It is also known that amphiphilic lipids form only one smectic phase in both thermotropic and lyotropic form. Since the smectic phase in thermotropic form of the amphiphilic lipids is similar or identical to their smectic phase in the lyotropic form, the amphiphilic lipid bilayers may be polarized even in the aqueous medium. Therefore, it is possible that the tilted lipids will give rise to ferroelectric domains in the biological cell membranes as well. As a result of in-plane anisotropy and ferroelectricity of the membrane, the lipid bilayer may play an active role in determining the excitable properties of the cell membrane.
Most proteins fold into unique three dimensional structures. The shape into which a protein naturally folds is known as its native state. There are four main protein structures known as primary, secondary, tertiary, and quaternary structures. In addition to the biochemical role of these main structures, proteins may shift between several related structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as “conformations,” and transitions between them are called conformational changes. For example, the binding of a substrate molecule to an enzyme results in such conformational changes in physical regions of the protein that participate in chemical catalysis. Discovering the tertiary and quaternary structure of protein complexes, can provide important clues about how the protein performs its function.
The main experimental methods of structure determination are X-ray crystallography and NMR spectroscopy, both of which can produce information at atomic resolution. At lower resolution, the cryo-electron microscopy is used to determine secondary structures of very large protein complexes such as virus coat proteins and amyloid fibers. A variant known as electron crystallography is also used in high-resolution studies in some cases, especially for two-dimensional crystals of membrane proteins. Solved structures are usually stored in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.
There are many more known gene sequences than there are solved protein structures. Further, the set of solved structures is biased toward those proteins that can be easily subjected to the experimental conditions required by one of the major structure determination methods. In particular, globular proteins are comparatively easy to crystallize in preparation for X-ray crystallography, which remains the oldest and most common structure determination technique. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB. Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for a protein whose structures have not been experimentally determined.